Nitric Oxide, Malnutrition and Chronic Renal Failure

Author(s): Tatiana M. C. Brunini, Monique B. Moss, Mariana A. S. Siqueira, Sergio F. F. Santos, Jocemir R. Lugon, Antonio C. Mendes-Ribeiro.

Journal Name: Cardiovascular & Hematological Agents in Medicinal Chemistry

Volume 5 , Issue 2 , 2007

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Abstract:

The conditionally essential amino acid L-arginine is the substrate for nitric oxide (NO) synthesis, a key second messenger involved in physiological functions including endothelium-dependent vascular relaxation and inhibition of platelet adhesion and aggregation. Extracellular L-arginine transport seems to be essential for the production of NO by the action of NO synthases (NOS), even when the intracellular levels of L-arginine are available in excess (L-arginine paradox). Chronic renal failure (CRF) is a complex clinical condition associated with accelerated atherosclerosis and thrombosis leading to cardiovascular events. Various studies document that markers of malnutrition and inflammation, such as low body mass index (BMI), C-reactive protein (CRP) and interleukin-6 (IL-6), are strong independent predictors of cardiovascular mortality in patients with end-stage renal disease (ESRD). There is considerable literature demonstrating that a disturbance in the nitric oxide control mechanism plays a role in mediating the haemodynamic and haemostatic disorders present in CRF. Endogenous analogues of L-arginine, ADMA and L-NMMA, which can inhibit NO synthesis and Larginine transport, are increased whilst L-arginine is reduced in plasma from all stages of CRF patients. In this context, the uptake of L-arginine in blood cells is increased in undialysed CRF patients and in patients treated by CAPD and haemodialysis. In platelets obtained from haemodialysis patients, the activation of L-arginine transport and NO production was limited to well-nourished patients.Impairment in nitric oxide bioactivity, coupled with malnutrition and inflammation, may contribute to increased incidence of atherothrombotic events in CRF. This article summarizes the current knowledge of L-arginine-nitric oxide pathway and malnutrition in CRF and briefly describes possible therapeutic interventions.

Keywords: L-arginine, nitric oxide, platelets, endothelium, malnutrition, chronic renal failure

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Article Details

VOLUME: 5
ISSUE: 2
Year: 2007
Page: [155 - 161]
Pages: 7
DOI: 10.2174/187152507780363214
Price: $58

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